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Tuesday, October 20, 2009

Ode to Peter Mitchell

Everyone knows about Watson & Crick and Albert Einstein and a few other famous scientists who have discovered something new.

But few people know Peter Mitchell and why he is more important than most other scientists.

Mitchell is one of a handful of scientists who really have changed the way we think about a subject—in this case how energy is produced in living cells [see PETER MITCHELL
AND CHEMIOSMOTIC THEORY]

Nick Lane has just published an article in New Scientist that highlights Mitchell's contribution to biochemistry. Not only did Peter Mitchell show us how chemical energy is produced in living cells, he also provided tremendous insight into how it must have worked when life first began [Was our oldest ancestor a proton-powered rock? ].

Here's the opening paragraphs of Nick Lane's excellent article. You really should read the whole thing—buy the magazine if you have to.

PETER MITCHELL was an eccentric figure. For much of his career he worked in his own lab in a restored manor house in Cornwall in the UK, his research funded in part by a herd of dairy cows. His ideas about the most basic process of life - how it gets energy - seemed ridiculous to his fellow biologists.

"I remember thinking to myself that I would bet anything that [it] didn't work that way," biochemist Leslie Orgel wrote of his meeting with Mitchell half a century ago. "Not since Darwin and Wallace has biology come up with an idea as counter-intuitive as those of, say, Einstein, Heisenberg and Schrödinger."

Over the following decades, however, it became clear that Mitchell was right. His vindication was complete when he won a Nobel prize in 1978. Even today, though, most biologists have yet to grasp the full implications of his revolutionary ideas - especially for the origin of life.

I wish this weren't so but I'm afraid the last statement is correct. It's not only biologists who fail to grasp the implications, there are even biochemists who don't understand chemiosmotic theory and don't teach it correctly in undergraduate courses.

Some of the most popular biochemistry textbooks didn't explain it properly until their most recent editions in 2006 and 2007. That's shocking.

Peter Mitchell deserves a lot more credit than he gets.

The molecule shown above is ubiquinone:cytochrome c oxidoreductase, also known as complex III [PDB 1PP9]. It is one of the most important enzymes in all of biology. It's structure provided the ultimate proof of chemiosmotic theory since it catalyzes the Q cycle, the key step in creating a proton gradient across a membrane [see Ubiquinone and the Proton Pump].

Every student who takes an introductory biochemistry course should be intimately familiar with this enzyme and how it works. In fact, if they're not, you can be sure that the biochemistry course was not taught properly.

5 comments
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I remember this enzyme always being presented as this random little thing hanging out in the membrane, overshadowed by the much larger neighbours (and larger = more interesting, obviously)

[rant]As a matter of fact, I can vividly remember this stuff being traumatically BORING. Even though in principle, the process that provides life access to energy to...happen... should actually be quite interesting. I've yet to come across any chemistry-related course being taught properly here, to be honest...

Our 300 lvl biochem (more macromolecular than the preceding intro course) is just *memorising* medically-relevant mammal-specific pathways, and which kinase phosphorylates which residue on which other random protein. I loathe biomed and anything to do with it, but this is labelled as a required 'general' course. But that's the least of the problems - they have turned something that could be fascinating like cell signalling and cell cycle regulation and turned it into a giant cramfest. And they try to cram so many facts (and factoids) into a three month course that there's simply no way you can soak all of that in properly. On top of 4-5 other courses, which also tend to be run exactly the same way. After all, they do explicitly cater to [vulgar adjectives] pre-meds. Because nothing can be as comforting as knowing that your doctors got there by memorising the textbook...

Also, that biochem course is where I recently heard 'This [ridiculously complicated kinase kinase kinase ... kinase pathway] evolved because it provides evolution plenty of elements to tweak with, so it can save energy when making new pathways'. TWITCH. I had to physically cover my mouth to not blurt out a stream of profanities... (to be fair, that was a TA during a tutorial. Still scary!)

The worst result of generally crappy teaching in a particular subject is that it turns you off from learning it properly on your own. I'm beginning to think it's much better to not be taught AT ALL than being taught shittily...[/rant]

Mitchell dubbed his theory chemiosmosis, and it is not surprising that biologists found it hard to accept. Why would life generate energy in such a complicated and roundabout way, when simple chemical reactions would suffice? It just didn't make sense.

There is no doubt that the common ancestor possessed DNA, RNA and proteins, a universal genetic code, ribosomes (the protein-building factories), ATP and a proton-powered enzyme for making ATP. The detailed mechanisms for reading off DNA and converting genes into proteins were also in place. In short, then, the last common ancestor of all life looks pretty much like a modern cell.

There are interested “fishing” parties out there who may well be reeling in those quotes!

When you do get time to "relearn" this, I have a suggestion: try to learn what was firmly KNOWN before the chemiosmotic hypothesis. Once you really do that, you will appreciate what a breakthrough in understanding things was Mitchel's theory. And how fundamental it is. The rest is simple math that you don't even need to memorize.

It was indeed a timely article. I knew all about chemiosmosis but not about the possible origin of life connections. I am off to see if the idea is stimulating much simulation work, but if you have any leads about that I'd be pleased to see them

Laurence A. Moran

Larry Moran is a Professor Emeritus in the Department of Biochemistry at the University of Toronto. You can contact him by looking up his email address on the University of Toronto website.

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The Sandwalk is the path behind the home of Charles Darwin where he used to walk every day, thinking about science. You can see the path in the woods in the upper left-hand corner of this image.

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Quotations

The old argument of design in nature, as given by Paley, which formerly seemed to me to be so conclusive, fails, now that the law of natural selection has been discovered. We can no longer argue that, for instance, the beautiful hinge of a bivalve shell must have been made by an intelligent being, like the hinge of a door by man. There seems to be no more design in the variability of organic beings and in the action of natural selection, than in the course which the wind blows.Charles Darwin (c1880)Although I am fully convinced of the truth of the views given in this volume, I by no means expect to convince experienced naturalists whose minds are stocked with a multitude of facts all viewed, during a long course of years, from a point of view directly opposite to mine. It is so easy to hide our ignorance under such expressions as "plan of creation," "unity of design," etc., and to think that we give an explanation when we only restate a fact. Any one whose disposition leads him to attach more weight to unexplained difficulties than to the explanation of a certain number of facts will certainly reject the theory.

Charles Darwin (1859)Science reveals where religion conceals. Where religion purports to explain, it actually resorts to tautology. To assert that "God did it" is no more than an admission of ignorance dressed deceitfully as an explanation...

Quotations

The world is not inhabited exclusively by fools, and when a subject arouses intense interest, as this one has, something other than semantics is usually at stake.
Stephen Jay Gould (1982)
I have championed contingency, and will continue to do so, because its large realm and legitimate claims have been so poorly attended by evolutionary scientists who cannot discern the beat of this different drummer while their brains and ears remain tuned to only the sounds of general theory.
Stephen Jay Gould (2002) p.1339
The essence of Darwinism lies in its claim that natural selection creates the fit. Variation is ubiquitous and random in direction. It supplies raw material only. Natural selection directs the course of evolutionary change.
Stephen Jay Gould (1977)
Rudyard Kipling asked how the leopard got its spots, the rhino its wrinkled skin. He called his answers "just-so stories." When evolutionists try to explain form and behavior, they also tell just-so stories—and the agent is natural selection. Virtuosity in invention replaces testability as the criterion for acceptance.
Stephen Jay Gould (1980)
Since 'change of gene frequencies in populations' is the 'official' definition of evolution, randomness has transgressed Darwin's border and asserted itself as an agent of evolutionary change.
Stephen Jay Gould (1983) p.335
The first commandment for all versions of NOMA might be summarized by stating: "Thou shalt not mix the magisteria by claiming that God directly ordains important events in the history of nature by special interference knowable only through revelation and not accessible to science." In common parlance, we refer to such special interference as "miracle"—operationally defined as a unique and temporary suspension of natural law to reorder the facts of nature by divine fiat.
Stephen Jay Gould (1999) p.84

Quotations

My own view is that conclusions about the evolution of human behavior should be based on research at least as rigorous as that used in studying nonhuman animals. And if you read the animal behavior journals, you'll see that this requirement sets the bar pretty high, so that many assertions about evolutionary psychology sink without a trace.

Jerry Coyne
Why Evolution Is TrueI once made the remark that two things disappeared in 1990: one was communism, the other was biochemistry and that only one of them should be allowed to come back.

Sydney Brenner
TIBS Dec. 2000
It is naïve to think that if a species' environment changes the species must adapt or else become extinct.... Just as a changed environment need not set in motion selection for new adaptations, new adaptations may evolve in an unchanging environment if new mutations arise that are superior to any pre-existing variations

Douglas Futuyma
One of the most frightening things in the Western world, and in this country in particular, is the number of people who believe in things that are scientifically false. If someone tells me that the earth is less than 10,000 years old, in my opinion he should see a psychiatrist.

Francis Crick
There will be no difficulty in computers being adapted to biology. There will be luddites. But they will be buried.

Sydney Brenner
An atheist before Darwin could have said, following Hume: 'I have no explanation for complex biological design. All I know is that God isn't a good explanation, so we must wait and hope that somebody comes up with a better one.' I can't help feeling that such a position, though logically sound, would have left one feeling pretty unsatisfied, and that although atheism might have been logically tenable before Darwin, Darwin made it possible to be an intellectually fulfilled atheist

Richard Dawkins
Another curious aspect of the theory of evolution is that everybody thinks he understand it. I mean philosophers, social scientists, and so on. While in fact very few people understand it, actually as it stands, even as it stood when Darwin expressed it, and even less as we now may be able to understand it in biology.

Jacques Monod
The false view of evolution as a process of global optimizing has been applied literally by engineers who, taken in by a mistaken metaphor, have attempted to find globally optimal solutions to design problems by writing programs that model evolution by natural selection.